Polydopamine-based loaded temozolomide nanoparticles conjugated by peptide-1 for glioblastoma chemotherapy and photothermal therapy

Purpose: Nanoparticles (NPs) of the polydopamine (PDA)-based,loaded with temozolomide (TMZ) and conjugated with Pep-1 (Peptide-1) as a feasible nano-drug delivery system were constructed and utilized for chemotherapy (CT) and photothermal therapy (PTT) of glioblastoma (GBM).Method: PDA NPs were synthesized from dopamine (DA) hydrochloride and reacted with TMZ to obtain the PDA-TMZ NPs and then the PDA NPs and the PDA-TMZ NPs were conjugated and modified by Pep-1 to obtain the Pep-1@PDA NPs and Pep-1@PDA-TMZ NPs via the Schiff base reaction (SBR), respectively.Their dimensions, charge, and shape were characterized by dynamic light scattering (DLS) and scanning electron microscope (SEM). The assembly of TMZ was verified by Fourier-transform infrared spectroscopy (FT-IR) and ultraviolet and visible spectroscopy (UV-Vis). The biostability of both the nanocarrier and the synthetic NPs were validated using water and fetal bovine serum (FBS). The antitumor activities of the PDA-TMZ NPs and Pep-1@PDA-TMZ NPs were verified in U87 cells and tumor-bearing nude mice.Results: The prepared PDA NPs, PDA-TMZ NPs, Pep-1@PDA NPs, and Pep-1@PDA-TMZ NPs were regular and spherical, with dimension of approximately 122, 131, 136, and 140 nm, respectively. The synthetic nanoparticles possessed good dispersity, stability,solubility, and biocompatibility. No obvious toxic side effects were observed, and the loading rate of TMZ was approximately 50%.In vitro research indicated that the inhibition ratio of the Pep-1@PDA-TMZ NPs combined with 808 nm laser was approximately 94% for U87 cells and in vivo research was approximately 77.13%, which was higher than the ratio of the other groups (p < 0.05).Conclusion: Pep-1 was conjugated and modified to PDA-TMZ NPs, which can serve as a new targeted drug nano-delivery system and can offer a CT and PTT integration therapy against GBM. Thus, Pep-1@PDA-TMZ NPs could be a feasible approach for efficient GBM therapy, and further provide some evidence and data for clinical transformation so that gradually conquer GBM

Association of heartbeat complexity with survival in advanced non-small cell lung cancer patients

BackgroundPrevious studies have shown that the predictive value of traditional linear (time domain and frequency domain) heart rate variability (HRV) for the survival of patients with advanced non-small cell lung cancer (NSCLC) is controversial. Nonlinear methods, based on the concept of complexity, have been used to evaluate HRV, providing a new means to reveal the physiological and pathological changes in HRV. This study aimed to assess the association between heartbeat complexity and overall survival in patients with advanced NSCLC.MethodsThis study included 78 patients with advanced NSCLC (mean age: 62.0 ± 9.3 years). A 5-min resting electrocardiogram of advanced NSCLC patients was collected to analyze the following HRV parameters: time domain indicators, i.e., standard deviation of the normal-normal intervals (SDNN) and root mean square of successive interval differences (RMSSD); frequency domain indicators, i.e., total power (TP), low frequency power (LF), high frequency power (HF), and the ratio of LF to HF (LF/HF); nonlinear HRV indicators characterizing heartbeat complexity, i.e., approximate entropy (ApEn), sample entropy (SampEn), and recurrence quantification analysis (RQA) indexes: mean diagonal line length (Lmean), maximal diagonal line length (Lmax), recurrence rate (REC), determinism (DET), and shannon entropy (ShanEn).ResultsUnivariate analysis revealed that the linear frequency domain parameter HF and nonlinear RQA parameters Lmax, REC, and DET were significantly correlated with the survival of advanced NSCLC patients (all p < 0.05). After adjusting for confounders in the multivariate analysis, HF, REC, and DET were found to be independent prognostic factors for the survival of patients with advanced NSCLC (all p < 0.05).ConclusionThere was an independent association between heartbeat complexity and survival in advanced NSCLC patients. The nonlinear analysis method based on RQA may provide valuable additional information for the prognostic stratification of patients with advanced NSCLC and may supplement the traditional time domain and frequency domain analysis methods

Assessment of short-term effects of thoracic radiotherapy on the cardiovascular parasympathetic and sympathetic nervous systems

BackgroundPrior research suggests that cardiovascular autonomic dysfunction might be an early marker of cardiotoxicity induced by antitumor treatment and act as an early predictor of cardiovascular disease-related morbidity and mortality. The impact of thoracic radiotherapy on the parasympathetic and sympathetic nervous systems, however, remains unclear. Therefore, this study aimed to evaluate the short-term effects of thoracic radiotherapy on the autonomic nervous system, using deceleration capacity (DC), acceleration capacity (AC) of heart rate, and heart rate variability (HRV) as assessment tools.MethodsA 5 min electrocardiogram was collected from 58 thoracic cancer patients before and after thoracic radiotherapy for DC, AC, and HRV analysis. HRV parameters employed included the standard deviation of the normal-normal interval (SDNN), root mean square of successive interval differences (RMSSD), low frequency power (LF), high frequency power (HF), total power (TP), and the LF to HF ratio. Some patients also received systemic therapies alongside radiotherapy; thus, patients were subdivided into a radiotherapy-only group (28 cases) and a combined radiotherapy and systemic therapies group (30 cases) for additional subgroup analysis.ResultsThoracic radiotherapy resulted in a significant reduction in DC (8.5 [5.0, 14.2] vs. 5.3 [3.5, 9.4], p = 0.002) and HRV parameters SDNN (9.9 [7.03, 16.0] vs. 8.2 [6.0, 12.4], p = 0.003), RMSSD (9.9 [6.9, 17.5] vs. 7.7 [4.8, 14.3], p = 0.009), LF (29 [10, 135] vs. 24 [15, 50], p = 0.005), HF (35 [12, 101] vs. 16 [9, 46], p = 0.002), TP (74 [41, 273] vs. 50 [33, 118], p < 0.001), and a significant increase in AC (−8.2 [−14.8, −4.9] vs. -5.8 [−10.1, −3.3], p = 0.003) and mean heart rate (79.8 ± 12.6 vs. 83.9 ± 13.6, p = 0.010). Subgroup analysis indicated similar trends in mean heart rate, DC, AC, and HRV parameters (SDNN, RMSSD, LF, HF, TP) in both the radiotherapy group and the combined treatment group post-radiotherapy. No statistically significant difference was noted in the changes observed in DC, AC, and HRV between the two groups pre- and post-radiotherapy.ConclusionThoracic radiotherapy may induce cardiovascular autonomic dysfunction by reducing parasympathetic activity and enhancing sympathetic activity. Importantly, the study found that the concurrent use of systemic therapies did not significantly amplify or contribute to the alterations in autonomic function in the short-term following thoracic radiotherapy. DC, AC and HRV are promising and feasible biomarkers for evaluating autonomic dysfunction caused by thoracic radiotherapy

Physiological effects of combined NaCl and NaHCO3 stress on the seedlings of two maple species

Salt stress impacts growth and physiological processes in plants, and some plants exposed to salt stress will produce physiological mechanisms to adapt to the new environment. However, the effects of combined NaCl and NaHCO3 stress on the seedlings of Acer species are understudied. In this study, we designed an experiment to measure physiological characteristics by establishing a range of NaCl and NaHCO3 concentrations (0, 25, 50, 75, and 100 mmol L-1) to estimate the compound salt tolerance of Acer ginnala and Acer palmatum. When the concentrations of NaCl and NaHCO3 were 25 mmol L-1, the leaf water content, relative conductivity, malondialdehyde (MDA) content, proline content, soluble sugar content, and chlorophyll did not change (p > 0.05) in two maple seedlings. At concentrations greater than 50 mmol L-1, the relative conductivity and MDA content increased, proline and soluble sugars accumulated, and the potential activity of PS II (Fv/Fo), potential photochemical efficiency of PS II (Fv/Fm), PS II actual photochemical efficiency (Yield), and photosynthetic electron transfer efficiency (ETR) decreased (p < 0.05). The superoxide dismutase (SOD) and catalase (CAT) activities showed the same trend of first increasing and then decreasing (p < 0.05). The peroxidase (POD) activity increased only when concentrations of NaCl and NaHCO3 were 100 mmol L-1, while there was no statistical difference between the other treatments and the control. Therefore, the two maple seedlings adjusted their osmotic balance and alleviated oxidative stress by accumulating proline, soluble sugars and increasing CAT and SOD activities. Further analysis showed that both species are salt tolerant and the salt tolerance of Acer ginnala is better than that of Acer palmatum

The Peculiarities of the Chinese Language and Methods of Its Teaching to Russian Students

В статье предпринимается попытка сопоставительного исследования особенностей китайского языка с точки зрения методики его преподавания как второго иностранного русским и зарубежным студентам в ТюмГУ. Для преодоления языковых препятствий в изучении и повышения качества его преподавания авторы предлагают различные учебные методы и способы, полезные для подготовки квалифицированных китаистов, преподающих китайский язык иностранным студентам. В ходе анализа и сопоставления выявлены языковые особенности китайского языка и разница между ним и русским в языковом семействе, а также указаны 4 больших языковых препятствия для русских студентов на первом этапе учебы и стратегия их . This paper is an attempt to do a comparative study which is focusing on different methods of teaching Chinese as a second foreign language to Russian and other foreign students at Tyumen State University. It is of great significance to overcome the language barrier while learning Chinese and enhance the Chinese teaching standard. Thus, the authors propose various teaching methods, contributing not only to teaching Chinese to Russian students and other foreign students, but also to sinologists for further study. In their comparative analysis the authors discuss linguistic features of the Chinese language and its dissimilarity with the Russian language; moreover, this article lists 4 major obstacles for the Russian students at the first stage of their studies, as well as the strategy to overcome them

BASI74, a Virulence-Related sRNA in Brucella abortus

Brucella spp. are intracellular pathogens that infect a wide variety of mammals including humans, posing threats to the livestock industry and human health in developing countries. A number of genes associated with the intracellular trafficking and multiplication have so far been identified in Brucella spp. However, the sophisticated post-transcriptional regulation and coordination of gene expression that enable Brucella spp. to adapt to changes in environment and to evade host cell defenses are not fully understood. Bacteria small RNAs (sRNAs) play a significant role in post-transcriptional regulation, which has already been confirmed in a number of bacteria but the role of sRNAs in Brucella remains elusive. In this study, we identified several different sRNAs in Brucella spp., and found that over-expression of a sRNA, tentatively termed BASI74, led to alternation in virulence of Brucella in macrophage infection model. The expression level of BASI74 increased while Brucella abortus 2308 was grown in acidic media. In addition, BASI74 affected the growth ratio of the Brucella cells in minimal media and iron limiting medium. Using a two-plasmid reporter system, we identified four genes as the target of BASI74. One target gene, BABI1154, was predicted to encode a cytosine-N4-specific DNA methyltransferase, which protects cellular DNA from the restriction endonuclease in Brucella. These results show that BASI74 plays an important role in Brucella survival in macrophage infection model, speculatively by its connection with stress response or impact on restriction-modification system. Our study promotes the understanding of Brucella sRNAs, as well as the mechanism by which sRNAs use to influence Brucella physiology and pathogenesis